Phenylketonuria

Phenylketonuria (PKU) is a rare genetic disorder with an incidence in the United States of about one in 10,000 to 15,000 births. PKU occurs when the body is deficient in the enzyme, phenylalanine hydroxylase, which converts the essential amino acid phenylalanine (Phe) to tyrosine. Although Phe is considered an essential amino acid, without the enzyme to convert it to tyrosine, the buildup of Phe in the blood can result in both physiological and neurological impairments, including intellectual disability. For individuals with this enzyme deficiency, serum levels of Phe need to be controlled and intake needs to be restricted in order to prevent lifelong impairments.

There is not a standard meal plan for PKU patients. Historically, children were treated with a low-protein diet; restricting dairy foods, meat, fish, poultry, eggs, legumes, and nuts, in addition to the sweetener aspartame. However, more modern research has indicated that adolescents and adults also benefit from following a Phe-restricted diet, along with consuming fortified, supplementary medical foods.

It is essential that an adequate intake of Phe-free formula and medical foods are consumed since they are the primary source of daily energy, amino acids (especially tyrosine), vitamins and minerals. In addition, it is important to provide adequate energy to avoid protein catabolism, which can elevate blood Phe levels.

Aside from overconsumption of dietary Phe, suboptimal intake of medical foods or catabolism during illness also can result in elevated blood Phe levels. The patient with PKU needs constant monitoring, adjusting and recalculating their meal plan to achieve appropriate balance.

While a Phe-restricted diet remains the cornerstone of treatment, new strategies have developed to improve metabolic control and compliance for the PKU patient.

Supplementation with the cofactor for Phe hydroxylase enzyme (BH4) has shown potential to increase Phe tolerance in patients with mild and classic PKU. And the use of large neutral amino acids (LNAAs) supplementation has been used to compete with Phe for transport into the brain. However, research has also suggested that LNAAs are even more effective when consumed in conjunction with a phe-restricted diet and not in place of it.

Another dietary food product, called glycomacropeptide (GMP), is derived from whey and contains a minimal amount of Phe after processing. Foods made with GMP provide an alternative to the amino acid medical foods currently required in the PKU diet. Studies have found GMP to be a safe option with minimal side effects and the potential to improve longer term adherence to a PKU diet due to improved satiety and acceptability.

Nutritional management in PKU must continue to develop alongside new treatments. There is not a simple one-plan-fits-all for the management of the PKU patient. Effective management requires a team approach with special expertise in PKU working closely with the family and individuals to achieve and maintain appropriate biochemical control, along with normal physical growth and cognitive function.

References:

• Escott-Stump, S. (2022). Phenylketonuria. In: Nutrition and Diagnosis Related Care, 9th Ed. Chicago, IL: Academy of Nutrition and Dietetics; 2022:248-251.
• Academy of Nutrition and Dietetics. Nutrition Care Manual®. Phenylketonuria (PKU). Accessed June 13, 2022.
• Manta-Vogli PD, Schulpis KH. Phenylketonuria Dietary Management and an Emerging Development. J Acad Nutr Diet. 2018;118(8):1361-1363.
• Douglas TD, Nucci AM, Berry AM, Henes ST, Singh RH. Large neutral amino acid status in association with P:T ratio and diet in adult and pediatric patients with phenylketonuria. JIMD Rep. 2019;50(1):50-59.